In murine fibroblasts, transfection of the v-FMS oncogenes has been reported to result in the development of platinum resistance. Although expression of the FMS (CSF-1 receptor) oncogene has been strongly correlated with presentations associated with poor prognosis in ovarian cancer, no link between platinum resistance and expression of this oncogene has been made in epithelial cancer. Preliminary data suggest that treatment of epithelial cancer cells that bear the CSF-1 receptor with CSF- 1 may induce this resistance. We and others believe that CSF-1 may act in epithelial cancer cells in a similar manner to its action in macrophages, with activation and invasive differentiation being an important components. It is the purpose of this proposal to further characterize the effects of CSF-1 treatment on FMS positive cells not only in regards to platinum resistance, but to its effect on levels of enzymes that scavenge reactive o2 species (ROS). Macrophage activation is signalled by enhanced oxidative metabolism, with release of ROS. Elevated glutathione levels is recognized to be one protective mechanism by which the cells cope with ROS formation, and is associated with platinum resistance in ovarian cancer. Other ROS scavenging enzymes have also been induced by similar processes. Thus measurement of these enzymes will be important in other agents that promote or interfere with macrophage activation act similarly to CSF-1, or modify CSF-1's effect on platinum resistance. In order to accomplish these aims we will transfect epithelial carcinoma cell lines with FMS to study the effect of ligand binding on sensitivity to platinum. Our long-term objectives would be to understand the molecular biology underlying platinum resistance in ovarian cancer and to develop long awaited therapeutics in this disease.